Role of nicotinic and estrogen signaling during experimental acute and chronic bladder inflammation

Magaly Martinez-Ferrer, Juan M. Iturregui, Consolate Uwamariya, Jonathan Starkman, Ali Reza Sharif-Afshar, Kichiya Suzuki, Wit Visedsindh, Robert J. Matusik, Roger R. Dmochowski, Neil A. Bhowmick

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Inflammation is a physiological process that characterizes many bladder diseases. We hypothesized that nicotinic and estrogen signaling could down-regulate bladder inflammation. Cyclophosphamide was used to induce acute and chronic bladder inflammation. Changes in bladder inflammation were measured histologically and by inflammatory gene expression. Antagonizing nicotinic signaling with mecamylamine further aggravated acute and chronic inflammatory changes resulting from cyclophosphamide treatment. Estrogen and nicotinic signaling independently attenuated acute bladder inflammation by decreasing neutrophil recruitment and down-regulating elevated lipocalin-2 and cathepsin D expression. However, the combined signaling by the estrogen and nicotinic pathways, as measured by macrophage infiltration and up-regulation of interleukin-6 expression in the bladder, synergistically reduced chronic bladder inflammation. The elevated expression of p65 nuclear localization in bladders treated with cyclophosphamide or cyclophosphamide with mecamylamine suggested nuclear factor-κB activation in the chronic inflammatory process. The complementary treat-ment of 17β-estradiol and the nicotinic agonist anabasine resulted in the translocation of p65 to the cytoplasm, again greater than either alone. Activation of nuclear factor-κB can result in macrophage activation and/or elevation in epithelial proliferation. These data suggest that 17β-estradiol and anabasine reduce chronic bladder inflammation through reduction of nuclear translocation of p65 to suppress cytokine expression.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalAmerican Journal of Pathology
Issue number1
Publication statusPublished - 2008 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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